The Emerging Link between O-GlcNAc and Alzheimer Disease

被引：200

作者：

Zhu, Yanping ^{[1
,2
]}

Shan, Xiaoyang ^{[1
]}

Yuzwa, Scott A. ^{[1
]}

Vocadlo, David J. ^{[1
,2
]}

机构：

[1] Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada

[2] Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2014年 / 289卷 / 50期

基金：

加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

Alzheimer Disease; Amyloid- (A); Brain Metabolism; Glucose Metabolism; Glycobiology; Glycoprotein; Glycosylation; O-GlcNAcylation; O-Linked N-Acetylglucosamine (O-GlcNAc); Tau Protein (Tau); AMYLOID PRECURSOR PROTEIN; PAIRED HELICAL FILAMENTS; TAU TRANSGENIC MICE; BETA-N-ACETYLGLUCOSAMINIDASE; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; MASS-SPECTROMETRY; COGNITIVE DECLINE; MOUSE MODEL; NUCLEOCYTOPLASMIC PROTEINS;

D O I：

10.1074/jbc.R114.601351

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Regional glucose hypometabolism is a defining feature of Alzheimer disease (AD). One emerging link between glucose hypometabolism and progression of AD is the nutrient-responsive post-translational O-GlcNAcylation of nucleocytoplasmic proteins. O-GlcNAc is abundant in neurons and occurs on both tau and amyloid precursor protein. Increased brain O-GlcNAcylation protects against tau and amyloid- peptide toxicity. Decreased O-GlcNAcylation occurs in AD, suggesting that glucose hypometabolism may impair the protective roles of O-GlcNAc within neurons and enable neurodegeneration. Here, we review how O-GlcNAc may link cerebral glucose hypometabolism to progression of AD and summarize data regarding the protective role of O-GlcNAc in AD models.

引用

页码：34472 / 34481

页数：10

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